May 7th, 2012

Difficulties and Differences on C difficile

Some things in our field — diseases, treatments, generalizations, cliches, fads — have really changed since back in the early 1990s, when I started in this business.

Here are a few that quickly come to mind:

  • “Double coverage” of pseudomonas with a beta lactam plus an aminoglycoside was de rigueur
  • MRSA was an inpatient concern only
  • You never saw Lyme disease in the winter or in people who hadn’t left urban areas
  • Mycobacterium avium complex was more of a problem in people with AIDS than in middle-aged, slender women who coughed
  • Kids still got epiglottitis and meningitis from H flu
  • Life-threatening colitis from C difficile was an exceedingly rare event, and barely ever occurred in otherwise healthy people

Yes, C diff has changed a lot — and not for the better. However, one thing that hasn’t changed about C diff  is the controversy over treatment, something we’re grappling with now.

Should initial therapy be metronidazole? Or vancomycin? Or vancomycin just for severe cases? Or fidaxomicin? What if cost were no issue?


How long should you treat, especially when the patient is still on antibiotics? What do you do about relapses? Probiotics? Tapering schedules? Fecal transplants? In severe cases, is diverting ileostomy an alternative to colectomy?

I don’t have the answers, just some opinions — which I’m happy to share — but first I’d be thrilled to get some outside views, if only on the initial therapy question.

5 Responses to “Difficulties and Differences on C difficile”

  1. todd ellerin says:

    First a disclaimer: As the wise Dr Robert(Bob)Rubin use to say (quoting one of his mentors), “there are 2 things in infectious diseases we don’t know….what to treat with and how long to treat for.”

    Here’s my 2012 opinion with respect to C. diff:
    1) Clinicians will look back on us some years from now and say ‘what were they thinking trying to treat antibiotic-induced colitis with antibiotics’
    2) The 2010 guidelines recommend metronidazole for mild cases of CDI and oral vanco for moderate-severe cases and IV mnz and oral/rectal vanco for fulminant cases. I think the guidance is reasonable but my gut still tells me that metronidazole should be reserved for your mother-in-law (Gorbach SL. Drugs for your mother-in-law, not your mother. Infect Dis Clin Pract 1992;1:46.) (Barza M. Metronidazole for Clostridium difficile: still only for your mother-in-law? Infect Dis Clin Pract 1997;6:211.)
    3)Fidaxomicin was recently approved for treatment of CDI and thus was not part of the 2010 treatment guidelines. If cost were no option, it would be a no brainer 1st line therapy since it has similar efficacy to oral vanco at day 10 (2 randomized trials) and is better than vanco at cutting down recurrences (roughly 50% less recurrences compared with oral vanco). Cost is an issue, though, so it remains to be seen where Fidaxo falls in our armamentarium. Insurers will dictate this. It should be noted that Fidaxo has the narrowest spectrum of activity against other bacteria (not active against gram negative bacteria (including Bacteroides) and has the lowest MIC against C. diff (unclear clinical relevance). In the clincial trials of oral Fidaxo v vacno, those individuals who received a dose of metronidazole prior to randomization did worse than those who did not receive any metronidazole
    4. It remains unclear where probiotics fit in for prevention of C. diff (Sacchromyces has shown more benefit than other probiotics but we need better studies). Most experts do not recommend probiotics while treating active CDI
    5. The tapering-pulse oral vancomycin regimen is recommended for patients who have a 2nd recurrence. This pulse part is supposed to allow the spores which are not killed by antibiotic to vegetate and then be killed by the abx. (this theory remains controversial). We don’t know whether substituting a 10 day course of Fidaxo in place of prolonged vanco will be any better (data free zone at this time)
    6. I am a huge proponent of fecal transplantation (from above via NGT or from below via colonoscope). The colonic bacterial milieu is really screwed up during CDI and the colonic flora is really complex (may be why probiotics aren’t the holy grail) so the theory of replacing sick stool with healthier stool is appealing 🙂 We just have to convince our patients of the appeal! If you have a patient that has failed multiple courses of vanco and now fidaxo, I strongly encourage you to refer your patient to the fecal transplant center nearest you.
    7. Last but not least decompressive/diverting ileostomy for severe complicated C. diff cases. To say that the Pittsburgh group got this one right is an underestimate (Ann Surg. 2011 Sep;254(3):423-7). I believe this study will revolutionize how we operate on our most severe cases of CDI. This observational study showed significant reductions in mortality and significant reductions in need for subtotal colectomy (compared with historical controls) and significant increases in future reanastomoses by avoiding subtotal colectomies and instead performing a decompressive ileostomy with 2 limbs (1 limb diverts the fecal stream and the other is used for intracolonic vanco). GoLytely is also given to washout the ‘evil humors’ and IV metronidazole is also given. Anectdotally, we have used this in about a half a dozen patients at my community hospital and the outcomes are remarkable. I’m thinking to myself that anyone who feels the need to study this as part of a randomized open label trial should abandon the urge and just do the less invasive procedure but I would never say that aloud in our era of evidence-based medicine. The subtotal colectomy will still be performed in the rare C. diff patient who has perforated.

    That’s my take on it…at least for today!

  2. I’d also recommend checking how long they have been on PPI or H2 antagonist therapy chronic use results in 3x higher incidence of c. diff occurrences in chronic PPI use and twice the incidence with H2 antagonist chronic use than the general population. Recommend using those agent intermittently for a couple of weeks at a time if absoulutely necessary and alter remaining drug therapy which may be necessitating chronic use of either of the tow agents.

  3. Sue says:

    As a former c. diff patient who takes PPIs, I’m thrilled to see this topic discussed. During multiple relapses, I went from metro to vanc to pulse/taper to rifaximin chaser. Rifaximin chaser is what made the difference. These days I’d want PCR-based testing, Fidaxo and possibly fecal transplant. In my experience, it has been doctors, not patients, who are squeamish about the fecal transplant. Many patients are desperate enough to do the transplant at home with or without physician support. Word still needs to spread about risks related to PPI use–and about the importance of hand washing (vs hand sanitizer) and use of bleach cleaning solutions to prevent transmission. When affordability of vanc is an issue, it can be delivered in a less-expensive form (oral solution) by compounding pharmacies.

    • Paul Sax says:

      Thanks to all (especially Todd — wow!) for your comments. I’ll share my thoughts shortly.


  4. PaulJosaph says:

    This disease is still a challenge. The cost associated to this is also very high.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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Infectious Diseases

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